Missing a specific blood group may genetically predispose people to obesity

ISLAMABAD, JUNE 27 (ONLINE): Researchers know that genetics play a role in obesity.
Scientists from the University of Exeter Medical School have found that people missing a specific blood group due to a genetic variant may be genetically predisposed to having obesity or overweight.

Researchers believe these people missing the SMIM1 gene may be treated using an already available drug for thyroid dysfunction.
While certain lifestyle factors play a role in obesity, researchers have realized that geneticsTrusted Source can also be an influencer.

For instance, a study presented earlier this year found children may inherit obesity from their parents. A study published in February 2023 linked 21 genesTrusted Source related to Alzheimer’s disease to obesity.

Now, scientists from the University of Exeter Medical School in England have found that people missing a specific blood group due to a genetic variantTrusted Source may be genetically predisposed to having obesity or overweight.

Researchers believe these people missing the SMIM1 geneTrusted Source may be treated using an already available drug for thyroid dysfunction.

The study was recently published in the journal MedTrusted Source.

Focusing on the SMIM1 gene
For this study, researchers used genetics data from about 500,000 people in the UK Biobank and four other cohorts to identify those with a genetic variant that turns off the SMIM1 gene.

“SMIM1 is a gene which encodes for a 68 amino acids protein, which on red cells sticks out of the cell membrane,” Mattia Frontini, PhD, associate professor of cell biology at the University of Exeter Medical School and lead author of this study explained to Medical News Today. “There is very little known about this gene. The family it belongs to is (a) collection of genes that have in common only the fact that (they) encode for short transmembrane proteins.”

“The initial discovery of the gene and its faulty copy 10 years ago was motivated by the need to develop a genetic test for a difficult-to-type using traditional methods blood group known as VelTrusted Source,” Frontini continued. “After this discovery was made, we discovered also that the differences in (these) genes that exist in the population are associated (with) tiny changes in the blood red cell parameters.”

Those without SMIM1 gene function more likely to be overweight
Using both genetic and blood sample data, Frontini and his team found that people with a loss of SMIM1 gene function were more likely to be overweight.

“We found that people with two faulty copies of the (SMIM1) gene — about 1 in 5,000 — are heavier than those who don’t [have it]. They have altered lipids in their blood and they use less energy given the same caloric intake. The excess [is] going [to be] stored as fat,” Frontini explained.

The researchers also found that people without SMIM1 gene function were more likely to display other measures linked to obesity including high levels of fat in the blood, signs of fat tissue dysfunction, and increased liver enzymes, as well as lower levels of thyroid hormones.

“What we found is that SMIM1 has an effect on the hypothalamus-pituitary-thyroid axis, which controls the production of many hormones. The absence of SMIM1 causes a mild form of hypothyroidism which results in reduced resting energy expenditure. In other words, these people use less energy given the same caloric intake — meal — which results in the excess being stored as fat. This is a common occurrence, almost 2% of the population in the U.K. receive thyroid supplementation, which is an effective and cheap treatment,” Frontini detailed.

“For the first time, we linked this gene [SMIM1] and its product to the metabolism control. Now further research is needed to determine if the gene is part of a completely novel pathway or if it feeds into one of the many known pathways that control metabolism.”
— Mattia Frontini, PhD

Further genetic research needed
After reviewing this study, Hans J. Schmidt, MD, director of the Center for Weight Loss and Metabolic Health and chief of Minimally Invasive and Bariatric Surgery at Hackensack University Medical Center in New Jersey told MNT there’s no question that in many cases obesity has a genetic cause.

“Some people easily gain weight and others eat whatever they want and never gain a pound. These are many genes involved in metabolism and fat storage but in some rare cases, a single genetic variant leads to obesity. This study shows there is evidence suggesting a link between a loss of function of the SMIM1 gene and excess weight. SMIM1 codes for a protein involved in regulating fat metabolism. In patients with no gene function, reduced energy expenditure leads to weight gain.”
— Hans J. Schmidt, MD

“The patients in this study were being studied for the genes coding a specific blood group,” he continued.

“The researchers incidentally found an association with obesity. The best next step would be to engage other researchers, studying other genetic traits, to see if there is (an) association between other genes and weight — both overweight and those not able to gain weight. The more we understand the genetic basis of obesity, the better we will be able to treat it,” Schmidt said.

Obesity is genetic and multifactorial
MNT also spoke with Mir Ali, MD, a board certified bariatric surgeon and medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, CA, about this study, which he said he found interesting.

“It’s something we’ve known for some time that there’s a big genetic component to obesity and it’s multifactorial — there’s not just one gene that contributes to being overweight. But our genetics and hereditary factors play a big role in obesity,” Ali said.

“If we can identify genetic variants that may be predisposed to obesity, we might be able to intervene at an earlier age and perhaps find some sort of medications and things that either block or overcome this genetic variant.”
— Mir Ali, MD

“(And) it’s not just one thing to identify the genetic variant, but what is the best treatment for this type of variant? Look at different modalities and see if there’s one thing or multiple things that might help these patients that are predisposed to obesity,” he added.